Deep brain stimulation using non-invasive techniques has long been a goal for therapeutic treatment of numerous disorders. As understood by those of skill in the art, deep brain regions, typically include those regions of the brain that are deeper into the brain that the outer cortical region of the brain, and particularly the region that is separated from the outer surface of the brain closest to the skull. In this context, deep brain regions may include, for example, the cingulate gyms and insula, thalamus, subthalamic nucleus, and globus pallidus.
It is widely believed in the field of Transcranial Magnetic Stimulation that the stimulation of deep brain target regions will require an increased level of stimulation because the magnetic flux falls off as a function of distance according to known principles. Thus, it is through that to effectively elicit firing of neurons from these deep brain structures, typically considered as triggering an action potential in the neural structure of the deep brain target, adequate stimulation must be received at the deep brain target; otherwise threshold for generating an action potential will not be achieved. The same principles may apply to the stimulation of neurons to hyperpolarize (inhibiting action potentials) or depolarize (making neurons more excitable). The threshold for stimulation of neurons (including deep brain targets) has historically been the motor threshold, which is the power required to activate an electromagnet coil to produce a motor response in a limb opposite the side of the motor cortex that is being stimulated by the coils (applied through the scalp and skull).
In the context of the present invention, typical deep brain target regions may include, for example, the insula and the cingulate gyms. Stimulation of a target deep brain regions without stimulating or depressing stimulation of nearby non-target brain region, and particularly brain regions between the target deep brain region and the TMS electromagnet, has previously been achieved by optimizing the power applied to the TMS electromagnet(s) so that the electromagnetic field(s) reaching the target and causing the fields to summate by one or more means including magnetic field overlap/superposition (physical summation), temporal summation, and spatial summation) to achieve the desired stimulation. Optimization typically means minimizing the power applied and using the best coil orientations and locations for delivery of each pulse from a TMS electromagnet so that the intervening non-target regions are not stimulated to the extent that non-intended effects either do not occur or are minimized.
Thus, power applied to any given electromagnet, and/or the rate that the power is applied, is preferably limited. However, the power applied by one or more TMS electromagnets intended to stimulate a deep brain target such as the insula or cingulate gyms must be sufficient to activate the deep brain target. While limiting the power and frequency applied to a target from a single stimulating location may protect structures superficial to the deeper target, it may be impossible to effectively stimulate a deep target because of the rapid fall off of the magnetic field. The attenuation of the magnetic field is commonly believed to be equivalent to roughly 1/(distance)2 at short distances This inverse-square relationship is particularly significant, because a version of this relationship has been used to determine the strength needed for stimulation of a deep brain target region by one or more TMS electromagnets. Known deep-brain stimulation techniques, including those described by Mishelevich and Schneider, have generally applied the inverse-square relationship to determine the stimulation power and/or frequency to be applied. As a result, the power predicted as necessary to stimulate structures further from the TMS coil (such as deep brain targets) has been widely held to be relatively large, particularly in light of the expectation that effective stimulation is achieved only when exceeding a threshold such as the motor threshold.
Herein we describe a system comprising an array of electromagnets configured to modulate activity of a deep-brain target when all of the TMS electromagnets in the system are operating at levels such that the summation at the target is below the motor threshold.